Glaucoma/DLK Inhibitors

Glaucoma/DLK Inhibitors

January 1, 2014: Califia Bio Inc. was awarded a $223,000 Phase 1 SBIR grant to develop inhibitors of Dual Leucine Zipper Kinase (DLK) for the treatment of glaucoma. This work involved a collaboration with the laboratory of Donald J. Zack M.D., Ph.D., Professor of Ophthalmology at Johns Hopkins University.

From funding from this collaboration we have identified a series of potent and very selective DLK inhibitors which are neuroprotective and promote retinal ganglion cell survival. We are working to develop these leads as potential treatments for glaucoma and other neurodegenerative diseases.

Glaucoma is the leading cause of irreversible blindness worldwide. In glaucoma, retinal ganglion cells (RGCs), the projection neurons that transmit vision from the retina to the brain, are injured and die, partially as a result of increased intraocular pressure (IOP). Current therapies (laser, surgery and eye drops) all act by lowering IOP. Unfortunately, lowering IOP can produce undesirable side effects and/or be difficult to achieve. The development of safe and efficacious neuroprotective agents would improve glaucoma therapy by complementing the currently available IOP treatment options. The Zack group at Johns Hopkins developed a high-content, high-throughput small molecule screen using mouse RGCs and identified the mixed lineage kinase DLK as a potential drug target. Potent Califia Bio DLK inhibitors are very active in the Johns Hopkins’ RGC protection assay and we have identified highly selective compounds for potential development as treatments for glaucoma.

We are seeking partners to develop and commercialize these compounds for Glaucoma treatments.

This research is supported by the National Eye Institute of the National Institutes of Healthunder Award Number R43EY024170. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National Institutes of Health.”